Prokineticin receptor-1 induces neovascularization and epicardial-derived progenitor cell differentiation

Kyoji Urayama, Célia Guilini, Gulen Turkeri, Selcuk Takir, Hitoshi Kurose, Nadia Messaddeq, Andrée Dierich, Canan G. Nebigil

研究成果: ジャーナルへの寄稿学術誌査読

68 被引用数 (Scopus)

抄録

OBJECTIVE - Identification of novel factors that contribute to myocardial repair and collateral vessel growth hold promise for treatment of heart diseases. We have shown that transient prokineticin receptor-1 (PKR1) gene transfer protects the heart against myocardial infarction in a mouse model. Here, we investigated the role of excessive PKR1 signaling in heart. METHODS AND RESULTS - Transgenic mice overexpressing PKR1 in cardiomyocytes displayed no spontaneous abnormalities in cardiomyocytes but showed an increased number of epicardial-derived progenitor cells (EPDCs), capillary density, and coronary arterioles. Coculturing EPDCs with H9c2 cardiomyoblasts overexpressing PKR1 promotes EPDC differentiation into endothelial and smooth muscle cells, mimicking our transgenic model. Overexpressing PKR1 in H9c2 cardiomyoblasts or in transgenic hearts upregulated prokineticin-2 levels. Exogenous prokineticin-2 induces significant outgrowth from neonatal and adult epicardial explants, promoting EPDC differentiation. These prokineticin-2 effects were abolished in cardiac explants from mice with PKR1-null mutation. Reduced capillary density and prokineticin-2 levels in PKR1-null mutant hearts supports the hypothesis of an autocrine/paracrine loop between PKR1 and prokineticin-2. CONCLUSION - Cardiomyocyte-PKR1 signaling upregulates its own ligand prokineticin-2 that acts as a paracrine factor, triggering EPDCs proliferation/differentiation. This study provides a novel insight for possible therapeutic strategies aiming at restoring pluripotency of adult EPDCs to promote neovasculogenesis by induction of cardiomyocyte PKR1 signaling.

本文言語英語
ページ(範囲)841-849
ページ数9
ジャーナルArteriosclerosis, thrombosis, and vascular biology
28
5
DOI
出版ステータス出版済み - 5月 2008

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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